title: CYP2B6*6 is associated with increased breast cancer risk.
abstract: The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of testosterone. Functional changes in this enzyme may influence endogenous hormone exposure, which has been associated with risk of breast cancer. To assess potential associations between two functional polymorphisms CYP2B6_516_G>T (rs3745274) and CYP2B6_785_A>G (rs2279343) and breast cancer risk, we established a specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay. The GENICA breast cancer case-control study showed associations between the variant genotypes CYP2B6_516_TT and CYP2B6_785_GG and breast cancer risk with odds ratios (ORs) of 1.34 (p = 0.001) and 1.31 (p = 0.002), respectively. A similar effect was observed for carriers of the CYP2B6_516_T allele in a validation study including four independent studies from Germany, Sweden and USA. In a pooled analysis of all five studies involving 4,638 breast cancer cases and 3,594 controls of European ancestry, carriers of the CYP2B6_516_G and the CYP2B6_785_G variant had an increased breast cancer risk with ORs of 1.10 (p = 0.027) and 1.10 (p = 0.031), respectively. We conclude that the genetic variants CYP2B6_516_G and CYP2B6_785_G (designated CYP2B6*6), which are known to decrease activity of the CYP2B6 enzyme, contribute to an increased breast cancer risk.
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Daniela
authors.initials: D
authors.lastname: Pentimalli
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rabstein
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Anne
authors.initials: A
authors.lastname: Lotz
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
authors.forename: Peter
authors.initials: P
authors.lastname: Schürmann
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Couch
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Lothar
authors.initials: L
authors.lastname: Häberle
authors.forename: Arif
authors.initials: A
authors.lastname: Ekici
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Kamilla
authors.initials: K
authors.lastname: Czene
authors.forename: Janjun
authors.initials: J
authors.lastname: Liu
authors.forename: Jingmei
authors.initials: J
authors.lastname: Li
authors.forename: Christian
authors.initials: C
authors.lastname: Baisch
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Yon-Dschun
authors.initials: YD
authors.lastname: Ko
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6
keywords: CYP2B6; breast cancer risk; polymorphism; testosterone